AUTHOR=Chen Fuying , Yao Lei , Zhang Xue , Gu Yan , Yu Hong , Yao Zhirong , Zhang Jia , Li Ming
TITLE=Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
JOURNAL=Frontiers in Genetics
VOLUME=12
YEAR=2021
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.736610
DOI=10.3389/fgene.2021.736610
ISSN=1664-8021
ABSTRACT=
Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in KRT5 and KRT14. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5. Biochemical experiments showed a mutation-induced alteration in the keratin 5 structure, intraepidermal blisters, and collapsed keratin intermediate filaments, but no quantitative change at the protein levels and interaction between keratin 5 and keratin 14. Moreover, we found that MAPK signaling was inhibited, while desmosomal protein desmoglein 1 (DSG1) was upregulated upon KRT5 mutation. Inhibition of EGFR phosphorylation upregulated DSG1 levels in an in vitro model. Collectively, our findings suggest that this mutation leads to localized recessive EBS and that keratin 5 is involved in maintaining DSG1 via activating MAPK signaling.